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Pharmaceutical Department
2014
Annual Report
2014 Annual Report
Pharmaceutical Department
Faculty • Full Members: William E. Evans, PharmD; William Greene, PharmD; Mary V. Relling,
PharmD (chair); Erin G. Schuetz, PhD; John D. Schuetz, PhD, Clinton F. Stewart, PharmD; Associate
Members: Sharyn D. Baker, PharmD, PhD; James Hoffman, PharmD; Alex Sparreboom, PhD;
Assistant Member: Jun J. Yang, PhD
Staff Scientists • Barthelemy Diouf, PhD; Ranjit Thirumaran, PharmD, PhD; Amarjit Chaudhry, PhD;
John Lynch, PhD; Shuiying Hui, PhD
Laboratory Directors • Alejandro Molinelli, PhD; Kristine R. Crews, PharmD
Fellows • Tamara Chang, MD; PhD; Satish Cheepala, PhD; Christina Drenberg, PhD; Christian
Fernandez, PhD; Yu Fukuda, PhD; Kevin Hicks, PharmD, PhD; ; Shangli Lian, PhD; Joseph
McCorkle, PhD; Steven Paugh, PhD; Virginia Perez-Andreu, MD, PhD; Aaron Pitre, PhD; Jessica
Morgan, PhD; Laura Ramsey, PhD; Jason Sprowl, PhD; Aisha Walker, PhD; Heng Xu,PhD; Aksana
Vasilyeva, PhD; Yuanyuan Zhang, PhD; Eric Zimmerman, PhD; Vinay Daryani, PharmD; Seth Karol,
MD; Navjotsingh Pabla, PhD; Yogesh Patel, PhD; Jolieke Van Oosterwijk, PhD, Maoxiang Qian, PhD;
Hui Zhang, MD,PhD
Residents •, Mark Dunnenberger, PharmD; Ben McDaniel, PharmD; Vanessa Millisor, PharmD; Diana
Wu, PharmD, Roseann Gammal, PharmD; Michael Dejos, PharmD, Courtney Watts, PharmD,
Joseph Sciasci, PharmD
Graduate Students • Chengcheng Liu; Rachel Scheib; Samit Ganguly; Rachel Ness, Adam Secrest;
Rebecca Quillivan; Takaya
Moriyama
Overview:
The primary goal of the
Pharmaceutical Sciences
Department is to improve therapy
for children with catastrophic
diseases by elucidating the basis for
interpatient variability in response
to medications. Survival rates for
children with cancer, HIV-1
infection, or other serious disease
continue to increase, largely
through the improved use of
medications. Failure of current
therapies and unacceptable adverse
effects are partly due to less-than
optimal medication dosing. Our
goal is to elucidate the biological
basis of interindividual differences
Figure 1. The Pharmaceutical Department encompasses basic, translational
and clinical research, and transitions innovative strategies into patient care.
in pharmacologic response, and to translate our findings into improving patient care.
Heterogeneity in the metabolism, transport, elimination, targets, and receptors of many drugs and
consequent variability in therapeutic or adverse effects may result from germline genetic differences
or genetic alterations in malignant cells. Drug response is also influenced by nongenetic factors
(e.g.,drug interactions, host organ function and maturity, disease severity, adherence to therapy).
We develop preclinical models to systematically characterize the determinants of human variation in
drug response, and we integrate our work into translational clinical studies (Figure 1). Laboratory
work informs
clinical studies, and
clinical problems
drive much of the
laboratory work.
Faculty members
lead and participate
in interdisciplinary
St. Jude programs
and national
cooperative
research
collaborations. Our
pharmacogenetic
research integrates
genome-wide
analyses, molecular
analyses, functional
genomics,
Figure 2. Post-doctoral fellows 2013-2014 Back row: Laura Ramsey, Jolieke Van Oosterwijk, Joseph
McCorkle, Vinay Daryani, Maxoxiang Qian, Navjotsingh Pabla, Seth Karol, Christian Fernandez,
pharmacokinetics,
Yogesh Patel Front row: Aaron Pitre, Jessica Morgan, Christina Drenberg,
and
Elixabet Lopez Lopez, Yu Fukuda, Yuanyuan Zhang, Hui Zhang
pharmacodynamics
to identify genetic determinants of drug effects, with the long- term goal of optimizing therapy for
individual patients. The Department comprises both Pharmaceutical Sciences and Pharmaceutical
Services, and includes ten faculty members, 15-25 post-doctoral fellows (Figure 2) and residents, 1020 undergraduate and graduate students, over 45 pharmacists, and over 106 full time staff members
working as computing experts, research nurses, technical, laboratory, administrative, and clinical
staff. The laboratory faculty members all have NIH-supported programs. The research in the
department includes clinical pharmacology, pharmacokinetics, pharmacodynamics, and
pharmacogenomics. Pharmaceutical Sciences occupies over 15,000 sq ft of contiguous state-of-theart equipped laboratory and office space, and Pharmaceutical Services occupies over 18,000 square
feet of space in the clinical areas of St. Jude. The department hosts weekly research workshops and
journal clubs that are open to the entire institution and are widely attended by colleagues outside the
department, in addition to multiple laboratory or Services specific meetings, webinars with national
and international colleagues, and regular pharmacogenomics meetings.
Details on the rich St. Jude environment for clinical care and for clinical and basic research are
available at www.stjude.org.
Pharmaceutical Department faculty, staff, and trainees work closely with each other; with our
collaborators in other departments at St. Jude; and with colleagues around the world on basic
translational, and clinical research projects and to provide outstanding pharmaceutical care to St.
Jude patients.
Faculty:
Sharyn D. Baker, PharmD, PhD
I have been a faculty member in the Pharmaceutical Sciences Department at St. Jude since 2006. The
majority of my research efforts have been focused on developmental therapeutics of childhood acute
myeloid leukemia (AML). A strong emphasis is placed on principles of clinical pharmacology
(pharmacokinetics, pharmacodynamics, pharmacogenetics, drug metabolism, drug transport, drug
interactions, adverse drug reactions) during all aspects of drug development with the goal of
optimizing therapy with investigational agents in children with cancer. We evaluate novel agents in
combination with standard AML chemotherapeutic agents such as cytarabine to assess for systemic
and intracellular pharmacokinetic and pharmacodynamic interactions, define the mechanisms of
interaction, and select
drug combinations that
demonstrate favorable
interactions and optimal
anti-leukemic activity. In
preclinical models, we are
evaluating histone
deacetylase inhibitors and
spliceosome modulaters
against high risk M7 AML,
and first- and secondgeneration FLT3
inhibitors against FLT3ITD-positive AML.
Clinically, we are
evaluating the multikinase inhibitor sorafenib
Figure 3. Factors affecting the systemic fate of sorafenib. Abbreviations: ABC, ATPbinding cassette transporters; β-GLU, β-glucuronidase; RTK, receptor tyrosine kinase;
with cytarabine-based
S-glu, sorafenib-glucuronide; SLC, solute carrier (S. Baker).
drug regimens in children
with newly diagnosed
FLT3-ITD positive AML and relapsed/refractory AML at St. Jude. The clinical problems observed with
sorafenib have driven new research projects in my laboratory including: to identify determinants of
sorafenib inter-patient pharmacokinetic variability, to determine the role of drug metabolism in the
anti-leukemic activity of sorafenib; to identify mechanisms involved in sorafenib-induced skin
toxicity; to identify mechanisms of sorafenib resistance in FLT3-ITD positive cases and identify new
agents for FLT3-ITD resistance. Figure 3 demonstrates our integrated approach to understand factors
affecting the pharmacokinetics and pharmacodynamics of sorafenib. Recent studies have identified
secondary FLT drug-resistant mutations in children with FLT3-ITD-positive AML receiving sorafenib
and sunitinib. Next generation sequencing has allowed us to monitor the emergence of low level
mutations, which is now guiding our preclinical in vivo studies to identify effective treatment
strategies for this disease. We use HPLC and mass spectrometric methods to study drug
pharmacokinetics, flow cytometry, multi-plexcytokine and phosphoprotein assays, and genomics to
study pharmacodynamics, cell culture models, molecular biologic techniques, murine models, and
analysis of clinical outcomes (toxicity and efficacy). We collaborate with many investigators within
the department, throughout St. Jude, and at Johns Hopkins University and Karmanos Cancer Institute.
William E. Evans, PharmD
Research in the Evans lab is focused on the pharmacogenomics of anticancer agents in children, with
an emphasis on childhood acute lymphoblastic leukemia (ALL) (reviewed in Evans and Relling,
Nature, 2004; Pui and Evans, NEJM, 2006; Paugh et al, Clin. Pharmacol. Ther. 2011). Several
approaches are currently being used to identify genes and genome variations that are important
determinants of the disposition and effects of antileukemic agents, including the interrogation of
candidate genes and the application of genome wide approaches such as gene expression profiling
(mRNA, microRNA) of leukemia cells, genome-wide SNP analyses (germline and somatic) and whole
exome/genome sequencing of patient cohorts that have been uniformly treated and evaluated on
prospective clinical trials at St. Jude Children's Research Hospital. During the past year, we focused
on identifying genomic determinants of the expression of genes in ALL cells that we previously
linked to de novo resistance to glucocorticoids, vincristine, asparaginase and mercaptopurine
(Holleman et al, NEJM, 2004; Lugthart et al, Cancer Cell, 2005; Diouf et al, Nature Med. 2011), and
genes linked to the intracellular disposition of high-dose methotrexate (Kager et al, JCI, 2005, Sorich
et al, PloS Medicine, 2008). These studies are building polygenomic models to elucidate the somatic
and inherited genome variants that influence inter-patient differences in the de novo sensitivity of
ALL cells to curative chemotherapy. We also completed a genome-wide analysis of germline SNPs
related to vincristine-induced peripheral neuropathy, leading to the identification of an inherited
variant in the promoter of CEP72, which encodes a centrosomal protein essential for microtubule
formation. The SNP creates a strong binding site for a transcriptional repressor (NKX6.3) leading to
lower expression, and enhanced sensitivity of iPSC neurons and human ALL cells to vincristine, a
microtubule inhibitor (Diouf et al, JAMA, 2015). Work in the lab is funded by a long-standing R37
from NCI (W Evans PI), a UO1 as part of the NIH-funded Pharmacogenetics Research Network (M.
Relling PI), by a Cancer Center Support grant from NCI, and by ALSAC. Going forward, our research is
designed to elucidate genomic determinants of toxicity and efficacy of antileukemic agents and to
translate this knowledge into new diagnostics and treatment strategies to optimize treatment of ALL
(see , Paugh et al, Clin Pharm. Ther. 2011; Dunnenberger et al, Ann Rev Pharmacol Tox, 2015).
William Greene, PharmD
I joined Pharmaceutical Sciences as Chief Pharmaceutical Officer in August 2007. I have had a long
career as a clinical pharmacy practitioner and leader in development of drug policy in hospital- based
practice. My interests have been diverse and are summed up in the goal of developing structures,
personnel, policy and practice to accomplish the best possible system to assure optimal outcomes of
pharmacotherapy. My interests in Infectious Disease, Pharmacokinetics, Performance Improvement
and Medication Safety continue.
As the senior leader of Pharmaceutical Services, it is my goal to assure the best possible design and
function of pharmacy services to assure that we achieve the desired outcomes of drug therapy for St.
Jude patients. Toward this end, Pharmaceutical Services collaborates closely with other disciplines in
providing patient care, and with clinicians and scientists in translational and clinical research, and
employs the principles of continuous process improvement in ongoing refinement/improvement of
patient-related services. Clinical research in Pharmaceutical Services has focused on collaboration in
applying pharmacokinetic, pharmacogenetic, and therapeutic drug monitoring principles to patient
care, and in improving the safety of medication use. I currently retain a faculty appointment with the
University of Tennessee College of Pharmacy (Professor, Affiliated), and am active in national and
state professional organizations (current member of the Board of Directors of Tennessee Pharmacists
Association).
James Hoffman, PharmD
I joined the Pharmaceutical
Department in 2004, and the St. Jude
Faculty in 2011. Through my role as
the Medication Outcomes & Safety
Officer for St. Jude I lead medication
use safety efforts across the hospital,
and I am dedicated to postgraduate
training by directing a specialized
residency program in MedicationUse Safety. My research is focused on
patient safety event detection,
patient safety culture, and clinical
decision support. Our work on
patient safety event detection and
reporting systems is built on our
department’s leadership to develop
and implement St. Jude’s novel
electronic event reporting system
(EERS) software. EERS is used to
report all patient safety events at St.
Jude, and this system has resulted in
a 20% increase in event reporting.
Because a healthy patient safety
culture is essential to safe care, we
have focused on assessing patient
safety culture at St. Jude and devised
new tools to measure specific
aspects of safety culture in the
hospital setting (Petschonek S et al J
Patient Saf 2014 and Burlison JD et al
Figure 4. Post-test alerts interrupt clinicians to change prescribing
J Patient Saf 2014). I also lead a
only when a high-risk drug is ordered for a patient with a high-risk
variety of efforts to expand and
pharmacogenetic phenotype. Clinical implementation of
pharmacogenetic tests is part of the medication safety program for
improve the use of clinical decision
St.
Jude (J. Hoffman).
support (CDS) in the electronic
health record (EHR) Through the
PG4KDS protocol, St. Jude is a leader in incorporating pharmacogenetic data and associated CDS into
the HER (Bell et al, JAMIA, 2013) (Figure 4), and I have contributed to this protocol as an investigator
since its inception.
Mary V. Relling, PharmD
I have been a faculty member in the Pharmaceutical Department at St. Jude since 1988. Since then, the
majority of my efforts have been directed to translational research in childhood acute lymphoblastic
leukemia (ALL), although I have also maintained clinical involvement at St. Jude and in the Children’s
Oncology Group (COG). The clinical problems faced by children with ALL drive my research. Much of
the work of my laboratory focuses on finding the genetic basis of why patients and their tumor cells
differ from one another. We also study how nongenetic factors (e.g., diet and drug interactions, kidney
and liver function, and age) affect how patients differ from each other in response to medications. The
ALL phenotypes we focus on most include relapse, glucocorticoid induced osteonecrosis (Figure 5)
And asparaginase immunogenicity and pharmacodynamics. Our laboratory has a heavy reliance on
computational
approaches, as we use
genome-wide tools to
interrogate genetic
variability. We also use
chemical analyses (e.g.
HPLC, LC/MS) to study
medication
pharmacokinetics, cell
culture models, molecular
biologic techniques,
murine models, and
analysis of clinical
outcomes and
phenotypes. In 2011, we
opened a clinical protocol,
PG4KDS, with the goal of
using array-based clinical
genotyping to implement
preemptive
pharmacogenetic tests
Figure 5. Higher serum anti-asparaginase antibody levels (over the first few months of
into clinical care for St.
therapy for ALL) are associated with a lower cumulative incidence of osteonecrosis
Jude patients (Bell et al,
(ON), shown for patients older than 10 years of age on the standard/high risk arms of St.
Jude trial Total XV (Liu et al Leukemia 2012). Higher antibodies translate into a lower
JAMIA 2013; Hicks et al
systemic exposure to both asparaginase and dexamethasone.
2012; Fernandez et al,
2012). We collaborate
with many investigators within the department, throughout St. Jude, within the COG, and within the
Pharmacogenomics Research Network (PGRN).
Erin G. Schuetz, PhD
I joined the St. Jude Pharmaceutical Sciences Department in 1993. My lab studies cytochromes P450
(CYP), enzymes that metabolize many of the drugs administered to St. Jude patients. The lab identifies
genetic determinants explaining variation in hepatic and intestinal CYP activities and, hence, variation
in drug efficacy, toxicity and, ultimately, therapeutic outcome. The lab strategically uses both the
candidate gene approach and exploits network and pathway analysis tools to illuminate the genetic
variation in novel candidate genes affecting the CYP genetic network. The liver system
biology/network approach has identified the node genes that, when individually perturbed, coregulate many genes in the CYP network. My lab then uses deep resequencing of these novel
candidate genes, and allelic expression imbalance analysis, to identify the functional and regulatory
variants responsible for altering CYP activity and driving changes in the CYP expression network.
Standard molecular, cellular and biochemical studies are then used to determine the functional
consequence of these variants. Retrospective association studies are performed to determine if
functional variants in candidate genes translate to clinical differences in CYP mediated drug clearance.
More recently our studies have focused on how drug transporters in the meningeal barrier layer
influence the disposition of drugs administered by intralumbar injection (intrathecally, IT) into the
cerebrospinal fluid (CSF). These studies were prompted by our unexpected discovery of high drug
transporter expression in the meningeal barrier cells lining the cranial and spinal CSF space.
However, there is a complete lack of understanding on how these transporters influence CSF and CNS
drug disposition and drug removal into the systemic circulation, despite the fact that the number of St.
Jude patients receiving IT chemotherapy continues to grow. Our studies include determining the
disposition of radiolabeled and fluorescent drugs administered IT to mice with and without drug
transporters and using confocal immuohistochemistry to determine transporter membrane location
in primary mouse leptomeningeal cells.
John D. Schuetz, PhD
A member of the Pharmaceutical Sciences Department since December 1992, my laboratory focuses
on understanding the contribution of ABC transporters to pathological processes and
pharmacological response using cell culture model systems as well as gene knockout models (e.g.,
reviewed Ann Rev Pharm Tox, 2006). Using these model systems, we have, through collaborative
effort with other SJCRH investigators identified one ABC transporter as an important stem cell marker
(Zhou et al, Nat Med, 2001, Zhou et al, PNAS, 2002) that has a prominent role in hematopoietic cell
Survival under hypoxia (Krishnamurthy et al, J Biol Chem, 2004). We extended these studies to
establish a knockout mouse which revealed for the first time that the ABC transporter (ABCC4/Mrp4)
was important in protecting the brain from penetration of chemotherapeutic agents (Leggas et al, Mol
Cell Biol, 2004). One could infer from these findings that the therapeutic efficacy of CNS-directed drugs
that are Mrp4 substrates may be improved by developing Mrp4 inhibitors. The ABCC4/Mrp4
transporter was first functionally defined by my laboratory (Schuetz et al, Nat Med, 1999) and more
recently was demonstrated to protect hematopoietic cells from injury due to the widely used
immunosuppressive and cancer chemotherapeutic agent 6-mercaptopurine. This finding allowed us
through collaborative efforts within the department (Evans, Relling, E. Schuetz) to identify a defective
ABCC4 allele that was prevalent in the Asian population, thus providing an explanation for the
anecdotal reports of enhanced sensitivity to the toxic hematopoietic side-effects of 6-mercaptopurine
in this population (Krishnamurthy et al, Cancer Res, 2008). More recent studies have focused on a
mitochondrial ABC transporter we first characterized (Krishnamurthy et al, Nature, 2006; Fukuda et
al, J Biol Chem, 2011) that protects cells from oxidative stress (Lynch et al, Cancer Res, 2009) and
appears to have a unique role in regulating other survival responses. Because over a third of ABC
transporters contribute to disease processes, our goal has been to understand the role of these genes
in pathological conditions. From this perspective recent studies have been focused on elucidating
how select ABC transporters contribute to leukemogenesis and therapeutic response.
Clinton F. Stewart, PharmD
I joined the Pharmaceutical Department at St. Jude in 1991, and since then have focused my research
efforts in developmental therapeutics for children with solid malignancies and central nervous system
tumors. In the clinic, my research involves the application of state of the art pharmacokinetic
(individual and population), pharmacogenetic, and pharmacodynamic approaches to understanding
the variability in drug disposition in children with cancer. Little is known about the disposition of
anti-cancer agents in infants and young children less than 3 years of age, which often leads to
increased risk of morbidity, poor tumor
control, and increased incidence of late effects.
Thus, we have embarked on a comprehensive
series of pharmacokinetic, pharmacogenetic,
and pharmacodynamic studies to understand
how developmental changes in infants and
young children affect the disposition and
toxicities of anticancer drugs used in the
treatment of infants with malignant brain
tumors. Our long-term goal is to determine
rational dosing regimens for infants and young
children by better understanding the
developmental pharmacology of anti-cancer
drugs and to apply these regimens to therapy
Figure 6. Schematic overview of our approach to using
Pharmacokinetic modeling and simulation in the identification of
for other childhood malignancies and chronic
new anticancer drugs for treatment of pediatric CNS tumors.
medical conditions. In addition to the studies
we perform at St. Jude, my lab collaborates
with investigators within the Pediatric Brain Tumor Consortium and the Children’s Oncology Group.
Our work in the laboratory is guided by addressing clinically relevant problems encountered in the
therapy of children with solid malignancies (e.g., effect of antiangiogenic drugs on cytotoxic drug
penetration) or brain tumors (e.g., CNS drug penetration in brain tumors). The studies in the lab are
designed to either yield data that can be translated into the design of improved clinical trials or to
answer questions generated in the clinic. For example, the treatment of children with primary central
nervous system (CNS) tumors continues to be a challenge despite recent advances in technology and
diagnostics. A variety of issues unique to pediatric CNS tumors impede development and clinical
success of novel therapies and for this reason safe and effective treatments remain elusive. The
preclinical approach we use (depicted in the Figure above) employs tumor subgroup-specific models
of pediatric CNS tumors, cerebral microdialysis sampling of tumor extracellular fluid (tECF), and
pharmacokinetic modeling and simulation to overcome challenges that currently hinder researchers
in this field.
Alex Sparreboom, PhD
I have been an associate member in the
Department of Pharmaceutical Sciences at St.
Jude since 2006. During the last 4-5 years, my
laboratory has studied mechanisms by which
anticancer agents accumulate in organs
involved in drug elimination, such as the
kidney and liver, and how that transport
process impacts interindividual variability in
drug response. We focus specifically on three
classes of specialized, membrane-localized
solute carriers, namely the organic cation
transporters (OCT) (Figure 6), organic anion
transporters (OAT), and organic anion
transporting polypeptides (OATP), and how
these carriers affect the disposition, organ
Figure 7. Detection of the transporter Oct2 by
immunohistochemistry in dorsal root ganglia of mice. Green,
Oct2; Blue, DAPI. (A. Sparreboom
specific toxicity and antitumor efficacy of various clinically important cancer drugs, such as platinumcontaining chemotherapeutics and tyrosine-kinase inhibitors.
We use cell-culture model systems, conditional gene knock-out/knock-in mouse models, and clinical
phenotype/genotype analyses to enhance understanding of interactions between cancer drugs and
uptake carriers of interest.
We actively collaborate with multiple investigators at St. Jude, Erasmus University, Johns Hopkins
University, Muenster University, Penn State College of Medicine, and University Hospital San Raffaele.
Jun J. Yang, PhD
I joined the St. Jude faculty in 2010 as an Assistant Member in Pharmaceutical Sciences, and the
research fo cu s o f m y group i s pharmacogenomics of treatment outcomes ( e.g. relapse) of
childhood acute lymphoblastic leukemia (ALL). Primarily taking a genome-wide approach, we
identify genetic variations that contribute to interpatient variability in response to ALL therapy.
By doing so, the goals of our research are to elucidate biological pathways dictating response to
antileukemic drugs, to identify genetic predictors for drug resistance which can be utilized for
treatment individualization, and to develop novel therapeutic agents to overcome drug resistance.
Because genetic factors in both host and tumor genome can affect drug response, my lab has
focused on characterization of inherited (germline) and acquired (somatic) genetic factors that are
associated with treatment response in childhood ALL. We h a v e l e d t h e f i r s t g e n o m e -wide
association study to identify germline genetic variations associated with minimal residual disease in
response to remission induction therapy in children with ALL (Yang et al, JAMA, 2009) and the first
genome-wide interrogation of copy number alterations related to ALL relapse (Yang et al, Blood,
2008). We are particularly interested in the genetic basis for racial/ethnic differences in ALL
treatment o u t c o m e s and disease susceptibility, e.g. we r e c e n t l y performed genome-wide
studies to characterize ancestry-related genetic variants that (Perez-Andreu et al, Nat Genet 2013, J
Clin Oncol 2012, J Natl Cancer Inst 2013) contribute to higher risk of relapse in Hispanic children
with ALL (Yang et al, Nat Genet, 2011). Our group is part of the NIH Pharmacogenomics
Research Network (PGRN) and the Pharmacogenomics of Anticancer Agents Research in Children
project (PAAR4Kids).
Pharmaceutical Services
Pharmaceutical Services is led by Dr. William Greene and is staffed by pharmacists, pharmacy
technicians, research and administrative staff, and faculty, (see Organization Chart at end) all
dedicated to helping patients. St. Jude Pharmaceutical Services is dedicated to providing the best
pharmaceutical care required for each child at SJCRH while supporting a collective research endeavor.
Our personnel, working with other caregivers in a cutting edge collaborative environment assure the
best possible outcomes of drug therapy. Over 110 pharmacists, technicians, and other support
personnel are involved in the care of patients and support of clinical research at St. Jude, helping to
fulfill our organizational mission to “advance cures, and means of prevention, for pediatric
catastrophic diseases through research and treatment.”
Pharmaceutical Services addresses St. Jude patients across the continuum of care – providing services
while they are inpatients, in the outpatient clinic, and while in domiciliary facilities or at home.
Inpatient services include Clinical Pharmacist collaboration in management of patients of all major
clinical patient care groups, including Leukemia/Lymphoma, Solid Tumor, Neuro-Oncology, Bone
Marrow Transplant, Hematology, and HIV services. After discharge from the hospital, these patients
are seen in outpatient clinics located on campus where pharmacists are directly involved with
Caregiver teams.
In these settings, pharmacists collaborate
in the care of these patients, including the
ordering of medications and laboratory
tests, the development of clinical
treatment protocols, provision of drug
therapy and nutritional support consults,
and assessment and management of the
long-term effects of medication therapy.
An on-site infusion center provides
medications for outpatients, and is fully
staffed by pharmacists. On average, there
are approximately 361 patient clinic
visits per day, with 103 infusion center
encounters, leading to the dispensing of
802 prescriptions or doses per day. An
inpatient census of approximately 47
patients per day requires more than 1600
Figure 8. Just for the CYP2D6 gene, 56 different diplotypes have been
dispensed doses per day. Nutrition
observed in the first 499 patients enrolled on the St. Jude clinical
support, pharmacokinetic,
protocol, PG4KDS. Each diplotype is translated into a phenotype; highrisk phenotypes drive drug prescribing (Hicks et al 2012).
Pharmacogenetic consults, (Figure 7) and
routine medication reconciliation at
discharge require direct pharmacist
involvement in patient care. Patients requiring intravenous therapy while outside the hospital are
managed through provision of therapy by the St. Jude Specialty/Home Infusion Pharmacy. This
service, initiated in early spring of 2011, was recognized by a Joint Commission surveyor as exhibiting
several “best practices” and having no recommendations for improvement during surveys in August of
2011 and November 2012. This service is now providing more than 340 doses per day, and is caring
for all St. Jude patients in the immediate service region.
At St. Jude, we provide the very best professional environment for pharmacists (Figure 8) – one that
supports growth and achievement of professional goals. Clinical Staff Pharmacists work from both
centralized and decentralized settings to collaborate with clinical providers in patient care. Clinical
Research Pharmacists, Informatics Pharmacists, and pharmacist leaders in medication outcomes and
medication safety work to assure optimal system support and design to facilitate the best outcomes of
patient care and clinical research. Certified Pharmacy Technicians collaborate with pharmacists to
assure excellence in operational functions. A technician career ladder has been developed, and
pharmacist developmental pathways provide internal opportunities for professional growth.
Professional society involvement is encouraged, and resources are dedicated to enhance professional
growth. St. Jude pharmacists play an active role in the Children’s Oncology Group, American College
of Clinical Pharmacy, American Society of Health-System Pharmacy, and many other professional
organizations.
St. Jude Pharmaceutical Services also collaborates closely with various colleges of pharmacy in
providing experiential education to pharmacy students. The department is formally affiliated with
the University of Tennessee (UT) College of
Pharmacy, but also works with students from
other colleges as they request the
opportunity. Members of the department
hold affiliated faculty appointments with the
UT College of Pharmacy. St. Jude pharmacy
personnel provide approximately 50
student-months of experience during an
academic year and 40 contact hours of
classroom training for UT pharmacy
students.
Pharmacists are integrated into each of the
major clinical services at St. Jude and stateFigure 9. Pharmacists are integral members of each of St.
of-the-art distribution and computer support
Jude’s clinical services.
systems assure efficient, effective delivery
and use of medications. Pharmacy
Information Systems is intimately involved in the maintenance and refinement of a complete
electronic medical record with computerized prescriber order entry and clinical decision support.
These same personnel lead efforts to identify and implement the best technology to ensure optimal
and safe patient outcomes.
Pharmacy Specialty Residencies
Trainees at St. Jude are supported by an
institutional Office of Academic Programs,
whose goal is to assist our investigators
and professional staff to improve the
quality of experiences, training, benefits,
and support for our undergraduate,
graduate, professional and postdoctoral
trainees. Over 300 post-doctoral trainees
(post-Ph.D, M.D, and Pharm.D.) are at St.
Jude, among whom are our PGY2 pharmacy
specialty residents. Our PGY2 residencies
in Pediatric Oncology, Medication Use
Safety, and in Pharmacogenomics are
accredited by the American Society of
Health System Pharmacists (ASHP).
Further details are available on St. Jude’s
website
(www.stjude.org/pharmacyresidency).
Figure 10. St. Jude PGY2 residents 2014-2015 (left to right): Michael
Dejos, PharmD, Courtney Watts, PharmD, Roseann Gammal, PharmD,
Joseph Sciasci, PharmD
Pharmacokinetics Shared Resources
The Pharmacokinetics Shared Resource is part of the NCI-designated Cancer Center, is housed within
Pharmaceutical Sciences laboratory space, is directed by Dr. Sharyn Baker, and provides centralized
high-quality, competitively funded, peer-reviewed pharmacokinetic/pharmacodynamics research in
both clinical and pre-clinical models at the St. Jude Cancer Center.
Our objectives are to facilitate:
Proper pharmacokinetic study design and implementation
Efficient and proper collection of biological samples for clinical pharmacokinetic and
pharmacodynamic studies
Implementation and quality control of sensitive and specific analyses of those samples for anticancer
drugs, their metabolites, or other relevant pharmacologic indices
The biomedical modeling of pharmacokinetic and pharmacodynamic data
Services include:
Protocol implementation (development of standard physician orders; building computerized
laboratory tests; refining sampling and processing procedures)
Research sample acquisition (centralized receiving, initial processing, storage, and distribution)
Analytical assay implementation and ongoing quality control, biomedical modeling, study design and
optimal sampling
Clinical Pharmacokinetics Laboratory
The Clinical Pharmacokinetics Laboratory (CPK lab), located in the Pharmaceutical Department
supports St. Jude’s mission by providing state of the art therapeutic drug monitoring and
pharmacogenetic testing that is interpreted by clinical pharmacists to assure optimal drug dosing. It is
directed by Dr. Alejandro Molinelli with translational support from Dr. Kristine Crews.
The Clinical Pharmacokinetics Laboratory is certified as a high complexity laboratory by CLIA and is
accredited by the College of American Pathologists. Our staff consists of licensed medical laboratory
scientists. Every year the laboratory will process and analyze approximately 8000 clinical specimens
and send-out another 300 to reference laboratories. The laboratory’s in-house test menu includes
multiple high-complexity assays ranging from therapeutic drug determinations (e.g.
immunosuppressant, antifungal drugs) to glomerular filtration rate estimation using 99mTc- DTPA.
Some of our resources include random access immunochemistry analyzers (e.g. Abbott Architect) and
analytical instrumentation (e.g. LC-MS/MS, GC/MS, HPLC). Most of our instruments have
bidirectional interfaces with the Cerner Millennium clinical informatics system. The laboratory also
handles pharmacogenetic testing for the hospital offering genotyping results that are always
accompanied by consults prepared by the clinical pharmacists or residents.
The laboratory staff and pharmacists at St. Jude work closely to provide results in a timely manner.
Once a test result is obtained the laboratory scientists alert the pharmacist, who in turn prepares a
clinical consult. This close integration of care assures that our patients receive the best treatment
while minimizing adverse effects from the drugs. The laboratory staff is also involved in clinical
translational science projects, for which tests developed in the research laboratories are validated and
incorporated into the CPK lab test menu as needed.
In addition to the samples for clinical testing, the CPK laboratory
staff members also process thousands of patient research
specimens a year, in support of various St. Jude research
protocols, for the Pharmacokinetics Shared Resource.
Pharmaceutical Department Publications 2013-2014
Barr J, Choughule K, Nepal S, Wong T, Chaudhry AS, Joswig-Jones CA, Zientek MA, Strom S, Schuetz
EG, Thummel K, Jones JP. Why do most human liver cytosol preparations lack xanthine oxidase
activity? Drug Metab Dispos 42(4):695-699, 2014. (PMCID: PMC3965898)
Bhatia S, Landier W, Hageman L, Kim H, Chen Y, Crews KR, Evans WE, Bostrom B, Casillas J, Dickens
DS, Maloney KW, Neglia JP, Ravindranath Y, Ritchey AK, Wong FL, Relling MV. Adherence to oral 6
mercaptopurine in African American and Asian children acute lymphoblastic leukemia – A Children’s
Oncology Group Study. Blood 124(15):2345-2353, 2014. (PMCID: PMC4192748)
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML,
Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV.
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic
leukemia. J Clin Oncol 32(9):949-959, 2014. (PMCID: PMC3948096)
Bhojwani D, Darbandi R, Pei D, Ramsey LB, Chemaitilly W, Sandlund JT, Cheng C, Pui CH, Relling MV,
Jeha S, Metzger ML. Severe hypertriglyceridemia during therapy for childhood acute lymphoblastic
leukemia. Eur J Cancer 50(15):2685-2694, 2014. (PMCID: PMC4180109)
Burger H, Den Dekker AT, Segeletz S, Boersma AWM, De Bruijn P, Debiec-Rychter M, Taguchi T,
Sleijfer S, Sparreboom A, Mathijssen RH, Wiemer EAC. Intracellular imatinib levels are primarily
determined by lysosomal sequestration. Br J Pharmacol, Submitted (February 2014).
Burlison JD, Scott SD, Browne EK, Thompson SG, Hoffman JM. The second victim experience and
support tool validation of an organizational resource for assessing second victim effects and the
quality of support resources. J Patient Saf, 2014.
Call RJ, Burlison JD, Robertson JJ, Scott JR, Baker DK, Rossi MG, Howard SC, Hoffman JM. Adverse drug
event detection in pediatric oncology and hematology patients: using medication triggers to identify
patient harm in a specialized pediatric patient population. J Pediatr Apr 24 doi:
10.1016/j.jpeds.2014.03.033. 2014. (PMCID: PMC4145034)
Caudle KE, Klein TE, Hoffman JM, Müller DJ Whirl-Carrillo M, Gong L, McDonagh EM, Sangkuhl K,
Thorn CF, Schwab M, Agúndez JA, Freimuth RR, Huser V, Lee MT, Iwuchukwu OF, Crews KR, Scott SA,
Wadelius M, Swen JJ, Tyndale RF, Stein CM, Roden D, Relling MV, Williams MS, Johnson SG.
Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics
Implementation Consortium (CPIC) guideline Development Process. Curr Drug Metab 15(2):209217, 2014. (PMCID: PMC3977533)
Jin D, Ni TT, Sun J, Wan H, Amack J, Yu G, Fleming J, Chiang C, Li W, Papierniak A, Cheepala S, Conseil
G, Cole S, Zhou B, Drummond I, Schuetz JD, Malicki J, Zhong T. Prostaglandin signaling regulates
ciliogenesis by modulating intraflagellar transport. Nat Cell Biol 16(9):841-851, 2014. (PMCID:
PMC4154319) Featured in News and Views in Nature Cell Biology
De Graan AJ, Sparreboom A, De Bruijn P, De Jonge E, Van der Holt B, Wiemer EAC, Verweij J, Mathijssen
RH, Van Schaik RH. 4β-Hydroxycholesterol as an endogenous CYP3A marker in cancer patients
treated with taxanes. Br J Pharmacol, Submitted (April 2014).
De Wit D, Gelderblom H, Sparreboom A, Den Hartigh J, Den Hollander M, Konig-Quartel JMC, Hessing
T, Guchelaar H-J, Van Erp NP. Midazolam as a phenotyping probe to predict sunitinib exposure in
patients with cancer. Cancer Chemother Pharmacol 73:87-96, 2014.
Demetz E, Schroll A, Auer K, Heim C, Patsch JR, Eller P, Theurl M, Lener D, Stanzl U, Theurl I, Seifert M,
Haschka D, Asshoff M, Sichtl S, Nairz M, Huber E, Stadlinger M, Li X, Pallweber P, Scharnagl H,
Stojakovic T, Marz W, Kleber ME, Garlaschelli K, Uboldi P, Catapano AL, Stellaard F, Rudling M, Kuba
K, Imai Y, Arita M, Schuetz JD, Pramstaller PP, Tietge U, Trauner M, Norata G, Claudel T, Hicks AA,
Weiss G, Tancevski I. The arachidonic acid metabolome as conserved regulator of cholesterol
metabolism. Cell Metab 20(5):787-798, 2014. (PMCID: PMC4232508)
Dering C, König IR, Ramsey LB, Relling MV, Yang W, Ziegler A. A comprehensive evaluation of
collapsing methods using simulated and real data: excellent annotation of functionality and large
sample sizes required. Front Genet 5:323, 2014. eCollection 2014 (PMCID: PMC4164031)
Diouf B, Crews KR, Lew G, Pei D, Cheng C, Bao J, Zheng JJ, Yang W, Fan Y, Wheeler HE, Wing C,
Delaney SM, Komatsu M, Paugh SW, McCorkle JR, Li X, Winick NJ, Carroll WL, Loh ML, Hunger SP,
Devidas M, Pui C-H, Dolan ME, Relling MV, Evans WE. Association of an inherited genetic variant
with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia.
JAMA, In Press
Dunnenberger HM, Crews KR, Hoffman JM, Caudle KE, Broeckel U, Howard SC, Hunkler RJ, Klein TE,
Evans WE, Relling MV. Preemptive clinical pharmacogenetics implementation: current programs in
five United States medical centers. Annu Rev Pharmacol Toxicol, 2014 Oct 2. [Epub ahead of print]
(PMID: 25292429)
Fernandez CA, Stewart E, Panetta JC, Wilkinson MR, Morrison AR, Finkelman FD, Sandlund JT, Pui CH,
Jeha S, Relling MV, Campbell PK. Successful challenges using native E. coli asparaginase after
hypersensitivity reactions to PEGylated E. coli asparaginase. Cancer Chemother Pharmacol
73(6):1307-1313, 2014. (PMCID: PMC4137479)
Fernandez CA, Smith C, Yang W, Date M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang
T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM,
Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is
associated with a higher risk of asparaginase allergies. Blood 124(8): 1266-1276, 2014. (PMCID:
PMC4141516)
Gajjar A, Stewart CF, Ellison DW, Kaste S, Kun LE, Packer RJ, Goldman S, Chintagumpala M, Wallace D,
TakebeN, Boyett JM, Gilbertson RJ, Curran T. Phase I study of vismodegib in children with recurrent
or refractory medulloblastoma: a pediatric brain tumor consortium study. Clin Cancer Res 19:63056312, 2013. (PMCID: PMC3856244)
Gurney JG, Bass JK, Onar-Thomas A, Huang J, Chintagumpala M, Bouffet E, Hassall T, Gururangan S,
Heath JA, Kellie S, Cohn R, Fisher MJ, Panadiker AP, Merchant TE, Srinivasan A, Wetmore C,
Qaddoumi I, Stewart CF, Armstrong GT, Broniscer A, Gajjar. Evaluation of amifostine for protection
for protection against cisplatin-induced serious hearing loss in children treated for average-risk or
high-risk medulloblastoma. Neuro Oncol 16(6):848-855, 2014. (PMCID: PMC4022215)
Hicks JK, Crews KR, Flynn P, Haidar CE, Daniels CC, Yang W, Panetta JC, Pei D, Scott JR, Molinelli AR,
Broeckel U, Bhojwani D, Evans WE, Relling MV. Voriconazole plasma concentrations in
immunocompromised pediatric patients vary by CYP2C19 diplotypes. Pharmacogenomics
15(8):1065-1078, 2014. (PMCID: PMC415556)
Hoffman JM, Haidar CE, Wilkinson MR, Crews KR, Baker DK, Kornegay NM, Yang W, Pui CH, Reiss UM,
Gaur AH, Howard SC, Evans WE, Broeckel U, Relling MV. PG4KDS: A model for the clinical
implementation of pre-emptive pharmacogenetics. Am J Med Genet C Semin Med Genet 166(1):4555, 2014. (PMCID: PMC4056586)
Hoffman JM, Frediani J, Herr M, Flynn PM, Adderson EE. The safety of cefepime and ceftazidime in
pediatric oncology patients. Pediatr Blood Cancer 60(5):806-809, 2013. (PMCID: PMC4006133)
Hoffman JM, Li E, Doloresco F, Matusiak L, Hunkler RJ, Shah ND, Vermeulen LC, Schumock GT.
Projecting future drug expenditures in U.S. nonfederal hospitals and clinics—2013. Am J Health Syst
Pharm 70(6):525-539, 2013. (PMID: 23456407. PMC: N/A)
Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A. Inhibition of OATP1B1 by tyrosine kinase
inhibitors: in vitro-in vivo correlations. Br J Cancer 110:894-898, 2014. (PMCID: PMC 3929889)
Kang G, Bi W, Zhao Y, Zhang J-F, Yang JJ, Xu H, Loh ML, Hunger SP, Relling MV, Pounds S, Cheng C. A
new system identification approach to identifying genetic variants in sequencing studies for a binary
phenotype. Hum Hered 78(2):104-116, 2014. (PMCID: 4270367)
Jones CL, Bhatla T, Blum R, Wang J, Paugh SW, Wen X, Bourgeois W, Bitterman DS, Raetz EA,
Morrison DJ, Teachey DT, Evans WE, Garabedian MJ, Carroll WL. Loss of TBL1XR1 disrupts
glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a Blymphoblastic leukemia model. J Biol Chem 289(30):20502-20515, 2014. Epub 2014 Jun 3. (PMID:
24895125) [PubMed - as supplied by publisher]
Kaste SC, Qi A, Smith K, Surprise H, Lovorn E, Boyett J, Ferry RJ Jr, Relling MV, Shurtleff SA, Pui CH,
Carbone L, Hudson MM, Ness KK. Calcium and cholecalciferol supplementation provides no added
benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute
lymphoblastic leukemia (ALL). Pediatr Blood Cancer, 2014. (PMID: 24395288)
Kaste SC , Pei D, Cheng C, Neel MD, Bowman WP, Ribeiro RC, Metzger ML, Bhojwani D, Inaba H,
Campbell P, Rubnitz J, Jeha S, Sandlund JT, Downing J, Relling MV, Pui C-H, Howard SC. Utility of early
screening magnetic resonance imaging for extensive hip osteonecrosis in pediatric patients treated
with glucocorticoids. J Clin Oncol, 2014. In Press.
Korf BR, Berry AB, Limson M, Marian AJ, Murray MF, O’Rourke PP, Passamani ER, Relling MV, Tooker
J, Tsongalis GJ, Rodriguez LL. Framework for development of physician competencies in genomic
medicine: report of the Competencies Working Group of the Inter-Society Coordinating Committee
for Physician Education in Genomics. Genet Med, 2014 April. (Epub ahead of print)
(PMID:24763287)
Lanvers-Kaminsky C, Sprowl JA, Malath I, Deuster D, Eveslage M, Schlatter E, Mathijssen RH, Boos J,
Jürgens H-J, am Zehnhoff-Dinnesen AG, Sparreboom A, Ciarimboli G. SLC22A2 c.808G>T carriers are
protected against cisplatin induced ototoxicity. Clin Pharmacol Ther, Submitted (March 2013).
Li E, Hoffman JM. Implications of the FDA draft guidance on biosimilars for clinicians: what we know
and don't know. J Natl Compr Canc Netw 11(4):368-372, 2013. (PMID: 23584340. PMC: N/A)
Lu C, Zhang J, Nagahawatte P, Easton J, Lee S, Liu Z, Ding L, Wyczalkowski MA, Valentine M, Navid F,
Mulder H, Tatevossian RG, Dalton J, Davenport J, Yin Z, Edmonson M, Rusch M, Wu G, Li Y, Parker M,
Hedlund E, Shurtleff S, Raimondi S, Bhavin V, Donald Y, Mardis ER, Wilson RK, Evans WE, Ellison DW,
Pounds S, Dyer M, Downing JR, Pappo A, Bahrami A. The Genomic Landscape of Childhood and
Adolescent Melanoma. J Invest Dermatol. 2014 Sep 30. doi: 10.1038/jid.2014.425. [Epub ahead of
print] PMID: 25268584
Lucio SD, Stevenson JG, Hoffman JM. Biosimilars: implications for health-system pharmacists. Am J
Health Syst Pharm 70(22):2004-2017, 2013. (PMID: 24173009)
Martin MA, Hoffman JM, Freimuth RR, Klein TE, Dong BJ, Pirmohamed M, Hicks JK, Wilkinson MR,
Haas DW, Kroetz DL. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for
HLA-B genotype and abacavir dosing: 2014 update. Clin Pharmacol Ther 95(5):499-500, 2014.
(PMCID: PMC3994233)
McBride A, Holle LM, Westendorf C, Sidebottom M, Griffith N, Muller RJ, Hoffman JM. National survey
on the effect of oncology drug shortages on cancer care. Am J Health Syst Pharm 70(7):609-617,
2013. (PMID: 23515514)
Morfouace M, Shelat A, Jacus M, Freeman BB 3rd, Robinson S, Turner D, Zindy F, Wang Y-D,
Finkelstein D, Bihannic L, Puget S, Ayrault O, Li X-N, Olson JM, Robinson GW, Guy RK, Stewart CF,
Gajjar A, Roussel MF. Pemetrexed and gemcitabine as combination therapy for the treatment of
group 3 medulloblastoma. Cancer Cell 25(4):516-529, 2014. (PMCID: PMC3994669).
Murphy AJ, Sarrezy V, Wang N, Bijl N, Abramowicz S, Welch CB, Schuetz JD, Yuan-Charvet L.
Deficiency of ATP binding cassette transporter B6 in Megakaryocyte progenitors accelerates
atheroschlerosis in mice. Arterioscler Thromb Vasc Biol 34(4):751-758, 2014. (PMID: 24504733;
PMCID: N/A)
Nies AT, Schaeffeler E, van der Kuip H, Cascorbi I, Bruhn O, Kneba M, Pott C, Hofmann U, Volk C, Hu S,
Baker SD, Sparreboom A, Ruth P, Koepsell H, Schwab M. Cellular uptake of imatinib into leukemic
cells is independent of human Organic Cation Transporter 1 (OCT1). Clin Cancer Res 20:985-994,
2014. (PMCID: PMC3932302)
Nieuweboer AJ, Hu S, Gui C, Hagenbuch B, Ghobadi Moghaddam-Helmantel IM, Gibson AA, De Bruijn
P, Mathijssen RH, Sparreboom A. Influence of drug formulation on OATP1B2-mediated transport of
paclitaxel. Cancer Res, 2014. In press.
Pabla N, Sprowl JA, Chen T, Du G, Lin W, Ong SS, Hu S, Gibson AA, Nies AT, Schwab M, Smital T,
Schlatter E, Ciarimboli G, Sparreboom A. Regulation of organic cation transporters by the tyrosineprotein kinase Yes. In preparation, April 2014.
Packer RJ, Rood BR, Turner DC, Stewart CF, Fisher M, Smith C, Young-Pouissant T, Goldman S, Lulla R,
Banerjee A, Pollack I, Kun L, Boyett JM, Onar-Thomas A, Wu S, Fouladi M. Phase I and
pharmacokinetic trial of PTC299 in pediatric patients with refractory or recurrent central nervous
system tumors: a PBTC study. J Neurooncol 121(1):217-224, 2015. PMID: 2540738
Perez-Andreu V, Roberts KG, Xu H, Smith C, Zhang H, Yang W, Harvey RC, Payne-Turner D, Devidas M,
Cheng IM, Carroll WL, Heerema NA, Carroll AJ, Raetz EA, Gastier-Foster JM, Marcucci G, Bloomfield
CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Rowe JM, Luger SM,
Tallman MS, Dean M, Burchard EG, Torgerson DG, Yue F, Wang Y, Pui CH, Jeha S, Relling MV, Evans
WE, Gerhard DS, Loh ML, Willman CL, Hunger SP, Mullighan CG, Yang JJ. A genome-wide association
study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults. Blood. 2014
Dec 2. [Epub ahead of print] (PMID: 25468567)
Pui C-H, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, Vora A, Baruchel A, Silverman LB,
Schmiegelow K, Escherich G, Horibe K, Benoit Y CM, Izraeli S, Yeoh AEJ, Liang D-C, Downing J, Evans
WE, Relling MV, Mullighan CG. Childhood acute lymphoblastic leukemia: progress through
collaboration. J Clin Oncol (In Press)
Petschonek S, Burlison J, Cross C, Martin K, Laver J, Landis RS, Hoffman JM. Development of the just
culture assessment tool: measuring the perceptions of health-care professionals in hospitals. J
Patient Saf 9(4):190-197, 2013. (PMCID: PMC4214367)
Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, Hudson MM, Ribeiro RC, Raimondi SC,
Jeha S, Howard SC, Bhojwani D, Inaba H, Rubnitz JE, Metzger ML, Gruber TA, Coustan-Smith E,
Downing JR, Leung WH, Relling MV, Evans WE. A revised definition for cure of childhood acute
lymphoblastic leukemia. Leukemia. 2014 Apr 30. [Epub ahead of print] (PMID: 24781017)
Ramsey LB, Janke LJ, Edick MJ, Cheng C, Williams RT, Sherr CJ, Evans WE , Relling MV. Host
thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine
model. Pharmacogenet Genomics 24(5):263-271, 2014. (PMCID: PMC4019208)
Relling MV, McDonagh EM, Chang T, Caudle KE, McLeod HL, Haidar CE, Klein T, Luzzatto L. clinical
Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the
context of G6PD deficiency genotype. Clin Pharmacol Ther 96(2):169-174, 2014. (PMCID:
PMC4111801)
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J,
Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS,
Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P,
Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL,
Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz
EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrózek K,
Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE,
Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL,
Zhang J, Mullighan CG. Targetable kinase activating lesions in ph-like acute lymphoblastic leukemia.
N Engl J Med 371(11):1005-1015, 2014. (PMCID: PMC4191900)
Roberts KG, Pei D, Campana D, Payne-Turner D, Li Y, Cheng C, Sandlund JT, Jeha S, Easton J, Becksfort
J, Zhang J, Coustan-Smith E, Raimondi SC, Leung WH, Relling MV, Evans WE, Downing JR, Mullighan
CG, Pui CH. Outcomes of children with BCR-ABL1-like acute lymphoblastic leukemia treated with
risk-directed therapy based on the levels of minimal residual disease. J Clin Oncol, 2014 Jul 21.
[Epub ahead of print] (PMCID: PMC4162497)
Roberts MS, Turner DC, Broniscer A, Stewart CF. Determination of crizotinib in human and mouse
plasma by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESIMS/MS). J Chromatography B 960C:151-157, 2014. (PMCID: PMC4062842).
Schuetz JD**, Swaan PW, Tweedie DJ. The role of transporters in toxicity and disease. Drug Metab
Dispos 42(4):541-545, 2014. (PMCID: PMC3965901) **corresponding author
Schully SD, Lam TK, Dotson WD, Chang CQ, Aronson N, Birkeland ML, Brewster SJ, Boccia S,
Buchanan AH, Calonge N, Calzone K, Djulbegovic B, Goddard KA, Klein RD, Klein TE, Lau J, Long R,
Lyman GH, Morgan RL, Palmer CG, Relling MV, Rubinstein WS, Swen JJ, Terry SF, Williams MS,
Khoury MJ. Evidence synthesis and guideline development in genomic medicine: current status and
future prospects. Genet Med, 2014 Jun 19. [Epub ahead of print] (PMID: 24946156)
Schumock GT, Li EC, Suda KJ, Matusiak LM, Hunkler RJ, Vermeulen LC, Hoffman JM. National trends in
prescription drug expenditures and projections for 2014. Am J Health Syst Pharm 71(6):482-499
2014. PMID: 24589540. PMC: N/A
Sprowl JA, Lancaster CS, Pabla N, Hu S, Hermann E, Kosloske A, Gibson AA, Zeeh D, Li L, Schlatter E,
Janke L, Ciarimboli G, Sparreboom A. Cisplatin-induced renal injury is independently mediated by
OCT2 and p53. Clin Cancer Res, 2014. In press.
Stewart CF, Tagen M, Schwartzberg LS, Blakely LJ, Tauer KW, Smiley LM. Phase I dosage finding and
pharmacokinetic study of intravenous topotecan and oral erlotinib in adults with refractory solid
tumors. Cancer Chemother Pharmacol 73(3):561-568, 2014. (PMCID: PMC3965853).
Tong WH, Pieters R, Kaspers GJ, Te Loo DM, Bierings MB, van den Bos C, Kollen WJ, Hop WC, LanversKaminsky C, Relling MV, Tissing WJ, van der Sluis IM. A prospective study on drug monitoring of
PEGasparaginase and Erwinia asparaginase and asparaginase antibodies in pediatric acute
lymphoblastic leukemia. Blood 123(13):2026-2033, 2014. (PMCID: PMC3968389)
Turner DC, Navid F, Daw NC, Mao S, Wu J, Santana VM, Neel M, Rao B, Willert JR, Loeb DM, Harstead
KE, Throm SL, Freeman BB III, Stewart CF. Population pharmacokinetics of bevacizumab in children
with osteosarcoma: implications for dosing. Clin Cancer Res 20:1-10, 2014. (PMCID: PMC4024352)
Touchette DR, Doloresco F, Suda KJ, Perez A, Turner S, Jalundhwala Y, Tangonan MC, Hoffman JM.
Economic evaluations of clinical pharmacy services: 2006-2010. Pharmacotherapy 2014 Mar 19.
doi:10.1002/phar.1414. (PMID: 24644086. PMC: N/A)
Walker AL, Lancaster CS, Finkelstein D, Ware RE, Sparreboom A. Organic anion transporting
polypeptide 1B (OATP1B) transporters modulate hydroxyurea pharmacokine-tics. Am Physiol Cell
Physiol 305:C1223-C1229, 2013.
Wang X, Liu W, Sun CL, Armenian SH, Hakonarson H, Hageman L, Ding Y, Landier W, Blanco JG, Chen
L, Quiñones A, Ferguson D, Winick N, Ginsberg JP, Keller F, Neglia JP, Desai S, Sklar CA, Castellino SM,
Cherrick I, Dreyer ZE, Hudson MM, Robison LL, Yasui Y, Relling MV, Bhatia S. Hyaluronan Synthase 3
Variant and anthracycline-related cardiomyopathy: a report from the Children's Oncology Group. J
Clin Oncol 32(7):647-653, 2014. (PMCID: PMC3927733)
Wang Z, Wong T, Hashizume T, Dickmann LZ, Scian M, Koszewski NJ, Goff JP, Horst RL, Chaudhry AS,
Schuetz EG, Thummel KE. Human UGT1A4 and UGT1A3 conjugate 25-hydroxyvitamin D3:
metabolite structure, kinetics, inducibility and interindividual variability. Endocrinology
155(6):2052-2063, 2014. (PMCID: PMC4020929)
Wilson CL, Liu L, Yang JJ, Kang G, Ojha RP, Neale G, Srivastava DK, Gurney JG, Hudson MM, Robison
LL, Ness KK. Genetic and clinical factors associated with obesity among adult survivors of childhood
cancer: A report from the St. Jude Lifetime cohort. Cancer, In press.
Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay NM, Wong
FL, Evans WE, Pui C-H, Bhatia S, Relling MV. Inherited NUDT15 variant is a genetic determinant of
mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol, In press.
ST. JUDE CHILDREN’S RESEARCH HOSPITAL - Pharmaceutical Department
Mary V. Relling, PharmD
CHAIR
Pharmaceutical Sciences
John Schuetz, PhD
Vice-Chair
Faculty
Sharyn Baker, PharmD, PhD
William Evans, PharmD
William Greene, BS, PharmD
James Hoffman, PharmD
Mary Relling, PharmD
Erin Schuetz, PhD
John Schuetz, PhD
Alex Sparreboom, PhD
Clinton Stewart, PharmD
Jun J. Yang, PhD
Postdoctoral Fellows
Vinay Daryani, PharmD
Christina Drenberg, PhD
Christian Fernandez, PhD
Yu Fukuda, PhD
Charnise Goodings, PhD
Seth Karol, MD
Robert McCorkle, PhD
Navjotsingh Pabla, PhD
Yogesh Patel, PhD
Virginia Perez-Andreu, MD, PhD
Aaron Pitre, PhD
Maoxiang Qian, PhD
Laura Ramsey, PhD
Jolieke Van Oosterwijk, PhD
Hui Zhang, MD, PhD
Yuanyuan Zhang, PhD
Staff Scientists
Amarjit Chaudhry, PhD
Barthelemy Diouf, PharmD, PhD
Shuiying Hu, PhD
John Lynch, PhD
Steven Paugh, PhD
Administrative
Jacquline Wicks-Callahan, MSOM, MBA
Admin Dir
Dawn Bowen, Office Manager
Caleb Simmons
Loretta McDowell, Admin Spec
Camille Miller, Admin Spec
Computing
Wenjian Yang, PhD
Colton Smith, PhD
Carl Panetta, PhD
Nancy Kornegay, MBA, Supervisor
Andrey Matlin
Clinical Research Nurses
Sheri Ring, BSN, Supervisor
Paula Condy, RN
Margaret Edwards, RN
Shannon Gibbs, RN
Teri Kuehner, RN
Melinda Wood, RN
Laboratory Staff
E. Bonten
D. Buelow
Y. Chu
M. Chung
P. McGill
C. Cline
X. DeMeter
G. Du
A. Davis
A. Kala
N. Lenchik
L. Li
Ting-Nien Lin
T. Moriyama
M. Needham
T. Owens
M.Payton
N. Selvo
S. Throm
A. Vasilyeva
Pharmaceutical Services
William Greene, BS Pharm, PharmD
Chief Pharmaceutical Officer
Clinical Lab
Alejandro Molinelli, PhD,
Director
Emily Melton, Supervisor
Krystal Effinger
Sherree Johns
Charles Rose
Laura Howell
Cathy Suggs
Administrative & Computing
Shaherah Yancy, MBA,
Admin Mgr
Yvonne Marshall, Admin Asst II
Dee Jackson, Admin Asst II
Christine Walters, Admin Spec.
Nekia Cole, HC-Pt. Rep
Laura Todd, Coord Pharm Billing
Murad Hasan, BS Pharm, MS
Pharmacogenomics
Kelly Caudle, PharmD, PhD
Kristine Crews, PharmD
Cyrine Haidar, PharmD
PK Shared Resource
Sharyn Baker, PhD, Director
Kristine Crews, PharmD, Co-Director
Paula Condy, RN
Jean DeMeter, PhD
Nancy Kornegay, MBA
Lie Li, PhD
Carl Panetta, PhD
Claire Patterson
Faculty Advisors/Collaborators
Mary Relling, PharmD
Alex Sparreboom, PhD
Clinton Stewart, PharmD
Medication Outcomes & Safety
James Hoffman, PharmD, Director
Jonathan Burlison, PhD
Delia Carias, PharmD
Jennifer Robertson, PharmD
Clinical Pharmacists
Allison Bragg, PharmD.
Sandy Call, PharmD
Delia Carias, PharmD
Richard Clark, PharmD
Shane Cross, PharmD
Sara Jane Faro, PharmD
David Gregornik, PharmD
Jennifer Pauley, PharmD
Jeff Scott, PharmD
Hope Swanson, PharmD
Deborah Ward, PharmD
Invest. Studies Pharm
Robbin Christensen, BS Pharm
Julie Richardson, PharmD
Linda Marden, BS Pharm, MS
Specialty Infusion Nurses
Debby Hrusa, RN
Ellie Thornton, BSN
Sr. Clin Staff Pharmacists
Susan Carr, PharmD
Shane Marshall, PharmD
Cheri Wilkerson, PharmD
Yolanda Williams, PharmD
Pharmacy Technicians
A. Gibson
E. Harstead
J. Hunt
M.Jacus
D. Jenkins
X. Zhao
Graduate Students
Samit Ganguly Chengcheng Liu
Rachel Ness
Y. Wang
H. Williams
K. Yasuda
Z. Yin
D. Black
J. Boeche
L. Bowman
R. Branum
M. Brittmon
S. Brittmon
D. Brooks
M. Brown
T. Bryant
D. Calhoun
H. Cash
R. Chapman
R. Connors
J. Cooper
P. Dorse
R. Garrett
B. Girdler
C. Greer
C. Henderson
T. Henderson
K. Hunter
P. Hunter
C. Johnson
E. King
D. Lewis
D. Lofton
N. Lundy
B. Macklin
K. McClelland
G. McDonald
K. McRae
E. McVey
S. Milan-Kizer
C. Moon
C. Radcliffe
N. Sims
T. Smith
P. Taylor
D. White
L. Wild
S. Williams
P. Woolbright
Student Interns
M. Brown
C. Daniels
S. Jain
M. Kinsella
J. Miller
H. Patel
E. Richardson
B. Shah
Directors
William Humphrey, BS Pharm, MS, MBA
John McCormick,BS Pharm, PharmD
Steve Pate, BS Pharm
Bruce Warren, BS Pharm, MS
Managers
Wendell Cheatham, BS Pharm
Barry Williams, BS Pharm
Clinical Staff Pharmacists
Chris Askins, PharmD
Monica Bant, PharmD
Patricia Bass, PharmD
James Bryant, BS Pharm
J. Monty Coleman, BS
Debra Ethridge, PharmD
Joseph Evans, PharmD
Amy Harris, PharmD
Timothy Jacobs, PharmD
Ed Jirik, BS Pharm
Jennifer Kemper, PharmD
Jenny Knych, PharmD
Chuck Longserre, PharmD
Christine Meisenheimer, PharmD
Anne McCormick, PharmD
Tommy Mills, PharmD
Jim Moore, BS Pharm
Elizabeth Moss, PharmD
Tiffany Nason, PharmD
Tanya Nguyen, PharmD
Trina Peery, BS Pharm
Jackie Quackenbush, BS Pharm
Christopher Scobey, PharmD
Matthew Wilson, PharmD
Curtis Yeh, PharmD
Clinical Pharmacist Residents
Ben McDaniel, PharmD
Vanessa Millisor, PharmD
Diana Wu, PharmD
3/31/2015